X-48901927-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong
The NM_001032382.2(PQBP1):c.180-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.58 ( 13103 hom., 18635 hem., cov: 22)
Exomes 𝑓: 0.61 ( 134857 hom. 222435 hem. )
Failed GnomAD Quality Control
Consequence
PQBP1
NM_001032382.2 splice_region, splice_polypyrimidine_tract, intron
NM_001032382.2 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.08010
2
Clinical Significance
Conservation
PhyloP100: 2.58
Genes affected
PQBP1 (HGNC:9330): (polyglutamine binding protein 1) This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. The encoded protein contains a WW domain. Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.[provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant X-48901927-C-T is Benign according to our data. Variant chrX-48901927-C-T is described in ClinVar as [Benign]. Clinvar id is 95309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-48901927-C-T is described in Lovd as [Benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PQBP1 | NM_001032382.2 | c.180-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000447146.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PQBP1 | ENST00000447146.7 | c.180-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001032382.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.579 AC: 63578AN: 109812Hom.: 13112 Cov.: 22 AF XY: 0.579 AC XY: 18602AN XY: 32138
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GnomAD3 exomes AF: 0.606 AC: 110628AN: 182555Hom.: 21111 AF XY: 0.618 AC XY: 41414AN XY: 67051
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GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.607 AC: 666188AN: 1097790Hom.: 134857 Cov.: 62 AF XY: 0.612 AC XY: 222435AN XY: 363180
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GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.579 AC: 63595AN: 109868Hom.: 13103 Cov.: 22 AF XY: 0.579 AC XY: 18635AN XY: 32204
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 07, 2018 | - - |
Renpenning syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
not specified Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 01, 2014 | - - |
History of neurodevelopmental disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2016 | This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at